Apparatus and methods for noninvasive monitoring of cancerous cells

ABSTRACT

A system for noninvasively monitoring cancerous cells within bodily fluid accumulated due to ascites, pleural effusion or pericardial effusion is provided including an implantable pump having control circuitry; a charging and communication system configured to periodically charge and communicate with the implantable pump to retrieve performance data; and monitoring and control software, suitable for use with conventional personal computers, for configuring and controlling operation of the implantable pump and charging and communication system. The implantable pump is configured to move fluid containing cancerous cells from a body cavity to the bladder such that the fluid may be excreted during urination, collected and analyzed with an analysis station to assess progress of the cancer or efficacy of a cancer treatment program.

I. CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part application of U.S. patentapplication Ser. No. 13/397,509, filed Feb. 15, 2012, and acontinuation-in-part application of U.S. patent application Ser. No.13/397,523, filed Feb. 15, 2012, both of which claim priority to U.S.Provisional Patent Application No. 61/443,668, filed Feb. 16, 2011, theentire contents of each of which are incorporated herein by reference.

II. FIELD OF THE INVENTION

This application relates to apparatus and methods for noninvasivemonitoring of cancerous cells in intracorporeal fluid accumulations.

III. BACKGROUND OF THE INVENTION

Certain cancers can result in pathologic chronic collection of bodilyfluids within cavities such as the peritoneum, pleura, or pericardialsac. Such cancers may cause chronic ascites, pleural effusion, orpericardial effusion, where chronic fluid collections persist and resultin increased morbidity and mortality.

In pleural effusion, excess fluid arising from an underlying pathology,such as lung cancer, breast cancer, melanoma, leukemia, or lymphoma,accumulates in the pleural cavity. If left untreated, the fluidaccumulation may interfere with proper lung function, significantlyincreasing morbidity and mortality.

In pericardial effusion, fluid accumulates in the pericardial sac andmay lead to increased intrapericardial pressure and reduced cardiacoutput. The excess fluid often results from an underlying cancer, suchas cancer that has metastasized to the pericardium, lung cancer, breastcancer, melanoma, leukemia, or lymphoma.

Ascites is a highly debilitating complication associated with manymedical conditions including liver failure, congestive heart failure,and certain cancers such as ovarian cancer, breast cancer, pancreaticcancer, uterine cancer, cancer of the bowels including colon cancer,melanoma, leukemia, or lymphoma. Untreated ascites can result inrespiratory compromise, compression of the inferior vena cava (a vitalblood vessel) and spontaneous bacterial peritonitis (a life-threateningcondition).

Treatment of cancer typically includes chemotherapy, radiation therapy,or medication infused in the area of the cancer. However, an effusionalso may be caused by cancer treatment, especially chemotherapy orradiation therapy.

A patient with cancer and ascites or an effusion, often caused by theunderlying cancer or cancer treatment, typically requirescontemporaneous treatment for both the cancer and the ascites/effusion.Conventional treatment for ascites, plural effusion, or pericardialeffusion involves one of three methods: 1) external drainage, whichposes a risk of infection and long-term requirement for multiplepunctures, 2) drainage to another body cavity, or 3) treatment withdrugs. Such methods suffer from a variety of drawbacks including highcost, continuous visits to a physician, ineffectiveness, and risk ofserious complications.

During treatment of cancer, it is imperative that a physician monitorthe progress of cancer cells. Using conventional methods, an invasivebiopsy of cancerous tissue generally is required to analyze the cancercells. A biopsy often must be sent to a remote laboratory for theanalysis, delaying the physician's ability to efficiently andeffectively treat the cancer.

In view of the above-noted drawbacks of previously-known systems, itwould be desirable to provide methods and apparatus for noninvasivemonitoring of cancerous cells while treating intracorporeal fluidaccumulation caused by ascites, pleural effusion, or pericardialeffusion.

IV. SUMMARY OF THE INVENTION

The present invention overcomes the drawbacks of previously-knownsystems for monitoring cancerous cells by providing a fluid managementsystem that automatically and autonomously moves fluid accumulationscontaining cancerous cells to the bladder with little patientinvolvement. Cancerous cells expelled via urination then are analyzed toassess progress of cancer treatment.

The fluid management system for expulsion of cancerous cells to permitnoninvasive monitoring of the cancerous cells preferably includes animplantable pump having a first controller; an inflow catheter having aninlet end adapted to be positioned within a body cavity and an outletend configured to be coupled to the implantable pump, the body cavityhaving an accumulation of fluid comprising cancerous cells; and anoutflow catheter having an inlet end configured to be coupled to theimplantable pump and an outlet end adapted to be positioned in abladder. The first controller preferably is programmed to selectivelyactivate the implantable pump to move the fluid comprising cancerouscells from the inlet end of the inflow catheter to the bladder duringpredetermined time periods.

The inlet end of the inflow catheter may be adapted to be positionedwithin the peritoneal cavity, the pleural cavity, or the pericardialcavity to treat conditions, such as ascites, pleural effusion, orpericardial effusion, arising from cancer or cancer treatment.

In accordance with one aspect of the present invention, a system fornoninvasive monitoring of cancerous cells is provided, including a fluidmanagement system configured to pump fluid containing cancerous cellsfrom a body cavity to the bladder and an analysis station configured toanalyze the cancerous cells excreted during urination. Preferably, thefluid management system includes an implantable pump having a firstcontroller; an inflow catheter having an inlet end adapted to bepositioned within a body cavity and an outlet end configured to becoupled to the implantable pump; and an outflow catheter having an inletend configured to be coupled to the implantable pump and an outlet endadapted to be positioned in a bladder. The first controller isprogrammed to selectively activate the implantable pump to move fluidthat includes suspended cancerous cells from the inlet end of the inflowcatheter to the bladder. The analysis station may be any conventionalsystem for analyzing cells to the presence or quantity of cancerouscells, and may be located remotely from the fluid management system orit may be located in close proximity. In one embodiment, the analysisstation is configured to analyze fluid including cancerous cellsexcreted from the bladder during urination to determine a parameterindicative of the progress of the cancer or an efficacy of a program totreat to the cancer.

The fluid management system may include an implantable device (alsoreferred to as an implantable pump), a controller, a battery and atransceiver; a charging and communication system configured toperiodically charge the battery of, and communicate with, theimplantable device; and monitoring and control software, suitable foruse with a conventional personal computer, for configuring andcontrolling operation of the implantable device and charging andcommunication system. Preferably, the monitoring and control software isavailable only to the treating physician, such that the patientgenerally interacts with the implantable device only via the chargingand communication system for purposes of recharging the implantabledevice. In accordance with one aspect of the present invention, theimplantable device is configured to pump fluid in small increments, atrelatively high flow rates, during predetermined times of the day toachieve a target volume, and further is configured to periodically alterthe pump position to reduce the risk of clogging of the implantabledevice during non-pumping intervals. The pump also may be programmed toperform a rapid sequence of backward and forward movements if a blockageis detected, thereby clearing the blockage. Additionally, the fluidmanagement system may include one or more sensors configured to detectindicia of the onset of infection, e.g., an increase in temperature,respiratory rate, or the viscosity of ascitic fluid, and one or morealarms configured to indicate to the physician a prediction or detectionof infection based on the output(s) of those sensors.

In one preferred embodiment, the implantable device includes anelectrically-driven mechanical gear pump configured for subcutaneousimplantation. The pump has an inlet port coupled to an inflow catheterand an outlet port coupled to a bladder catheter. In accordance with oneaspect of the present invention, the pump employs a pair of floatinggears that function as a positive displacement pump, wherein a drivinggear is coupled to a splined shaft of an electric motor to minimizepower consumption arising due to manufacturing variations or shafteccentricity. The inflow catheter comprises a tube having a first endconfigured to be coupled to the pump inlet and a second end configuredto be positioned in a selected cavity, e.g., peritoneum, pleura orpericardial sac. The second end of the inflow catheter includes aplurality of through-wall apertures that permit fluid accumulating topass into the catheter. The bladder or outflow catheter comprises a tubehaving a first end configured to be coupled to the pump and a second endconfigured to be inserted through the wall of, and fixed within, apatient's bladder. The fluid circuit further includes sensors arrangedto monitor ambient pressure, pressure at the pump inlet, pressure at thepump outlet, pressure in the bladder, and optionally the temperature ofthe ascitic fluid and the respiratory rate of the patient. The inflowand outflow catheters include connectors configured to reduce the riskof improper implantation.

The implantable device further comprises a controller, packaged togetherwith the pump, electric motor, battery, charging coil, and radiotransceiver within a low volume sealed housing. The controller iscoupled to the pump motor, battery, transceiver and a plurality ofsensors to continually monitor pressure, temperature, humidity, chargestatus, pump status, patient movement and other environmental and systemrelated parameters. The controller preferably comprises a processor,nonvolatile memory for storing firmware, implant identificationinformation, and system and environmental data, and volatile memory thatserves as a buffer for computations and instructions during executionand firmware updating. The pump motor is configured for extended use andlow power consumption, and preferably includes Hall effect sensors forposition sensing and to determine the direction of rotation (andcorrespondingly, flow and fluid viscosity). The battery preferably is along-lasting lithium-ion or lithium polymer battery that is coupled toan inductive charging circuit, thereby enabling the battery to berecharged using the external charging and communication system. A radiofrequency transceiver preferably is employed in the device fortransmitting system information to, and receiving information from, theexternal charging and communication system, including system performancedata, commands, and firmware upgrades. All of the foregoing componentspreferably are disposed within the housing, which further includes afiller having a low permeability for water, thereby reducinginfiltration of moisture into the housing.

In accordance with one aspect of the present invention, the fluidmanagement system includes an external charging and communicationsystem. In a preferred embodiment, the charging and communication systemcomprises a housing containing a controller, radio transceiver,inductive charging circuit, power source and quality-of-chargingindicator. The controller is coupled to the inductive charging circuit,power source, quality-of-charging indicator, radio transceiver, andmemory for storing information to be transmitted between the monitoringand control software and implantable device. The charging andcommunication system preferably includes a data port, such as a USBport, or a wireless port, such as Bluetooth, Zigbee or GPRS, thatpermits the charging and communication system to be coupled to aconventional computer, such as a personal computer or laptop computer,configured to run the monitoring and control software. In oneembodiment, the charging and communication system may include a cordthat enables the system to be directly coupled to a conventional powersupply, such as 120V AC wall socket. More preferably, however, thecharging and communication system includes a battery-powered handpiecethat periodically may be coupled to an AC powered charging base, so thatthe handpiece may be separated from the base to recharge the implantabledevice without tethering the patient with a power cord. In one preferredembodiment, the control circuitry of the charging and communicationsystem may be configured to boost power supplied through the inductivecharging circuit to the motor of the implantable device to unblockpotential clogging of the gear pump.

The fluid management system further comprises monitoring and controlsoftware that preferably is accessible only to the patient's physician.The software is configured to run on a conventional personal computer orlaptop computer, and enables the physician to configure and monitoroperation of the charging and communication system and implantabledevice. The software may include routines for controlling any of anumber of parameters associated with the pump operation, such as atarget amount of fluid to move daily or per motor actuation, and limitsfor inflow catheter pressure, bladder pressure, pump pressure, andimplant temperature. The software also may be configured to controloperation of the implantable device so as not to move fluid duringspecific periods (e.g., at night) or to defer pump actuation if thepatient is asleep. The software further may be configured, for example,to send immediate commands to the implantable device to start or stopthe pump, or to operate the pump in reverse or at high power to unblockthe pump or its associated catheters, such as when the patient isvisiting his or her physician. The software may be configured todownload data collected from the implantable device and stored on thecharging and communication system, such as during a patient visit to thephysician's office. Optionally, based on the downloaded information,such as the patient's respiratory rate, temperature, and fluidviscosity, the software may be configured to alert the physician of aprediction or detection of infection.

It is contemplated that the system of the present invention may avoiddifficulties typically associated with the previously-known apparatusand methods for addressing ascites. It is expected, for instance, thatthe system and methods of the present invention will enable smallquantities of peritoneal fluid to be moved to the bladder without theinconvenience and complications generally associated with use ofpharmaceuticals or paracenteses. In particular, because the apparatusand methods of the present invention avoid repeated, periodic removal oflarge quantities of fluid, as occurs with paracenteses, the tendency togenerate additional ascites to offset the removed fluid will be reduced.These effects in turn are expected to obviate the need to infuse plasmaexpanders, such as human albumin, into the patient followingparacentesis, thereby resulting in significant cost savings to thepatient and health care system. The prediction or detection ofinfection, particularly at an early stage of infection, further mayimprove patient outcomes and reduce the need for more expensivetreatments. Finally, the apparatus and methods of the present inventionare expected to provide improved quality of life for chronic ascitespatients, allowing such patients to pursue less sedentary lifestylesthan would otherwise be possible, and encouraging better compliance withmedically-directed dietary and exercise regimes.

In an alternative embodiment, a fluid management system is providedgenerally as described above, but instead configured for treatingpleural or pericardial effusion arising from cancer or cancer treatment.Few surgical options are available for treating these conditions, andmost of those present significant risks for morbidity and morality. Inparticular, the system of the present invention may be configured fortreating pleural or pericardial effusion, and comprises an implantabledevice, a charging and communication system and software substantiallyas described above. This embodiment differs from the ascites fluidmanagement system of the present invention primarily in that the pumphas an inflow catheter coupled to a pleural or pericardial cavity andthe controller is configured to work under negative pressures. Moreparticularly, the inflow catheter has a first end configured to becoupled to the pump inlet and a second end configured to be positionedin the pleural or pericardial cavity, and includes a plurality ofthrough-wall apertures that permit fluid accumulating in the cavity topass into the catheter without interfering with proper functioning ofthe lungs or heart. As some fluid is required to lubricate movement ofthe organ within these cavities, the implantable device preferably isprogrammed not to pump all of the fluid from the cavity. In addition,the implantable device is programmed to interpret and provide drainagethat accounts for pressure fluctuations arising in the cavity duringnormal respiration or cardiac activity.

Methods of implanting and operating the fluid management system of thepresent invention also are provided. The implantable device preferablymay be placed subcutaneously using interventional radiologic techniquesincluding radiographic imaging or ultrasound, while the inflow catheterand outflow catheter may be placed using surgical, or more preferably,minimally invasive procedures. The inflow catheter, in one variation,may be tunneled subcutaneously to the site of drainage and the outflowtubing can be subcutaneously channeled to the bladder (or peritonealcavity). The implantable device preferably is programmed using radiofrequency coupling of the transceivers in the implantable device andcharging and communication system, while power is supplied to thebattery of the implantable device by coupling the inductive chargingcircuits of the implantable device and charging and communicationsystem. Additional details of methods of implanting and operating asystem in accordance with the present invention are described below.

In accordance with one aspect of the present invention, a method fornoninvasive monitoring of cancerous cells is provided. The methodincludes pumping, via an implantable pump, bodily fluid comprisingcancerous cells from a body cavity having an accumulation of the bodilyfluid to the bladder for excretion; and collecting cancerous cellsexcreted from the bladder for analysis. Such preparation may include,for example, receiving a urination sample, transferring a urinationsample to a physician, transferring a urination sample to a local orremote analysis station. The method further may include analyzing thecancerous cells to determine a parameter indicative of progress of thecancer or efficacy of a cancer treatment program, for example, using theanalysis station, to detect the presence or quantity of cancerous cellsin the patient's urine.

V. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of the components of an exemplary fluidmanagement system and an exemplary analysis station constructed inaccordance with the principles of the present invention.

FIGS. 2A and 2B are, respectively, side view and perspective detailedviews of an exemplary embodiment of an inflow catheter suitable for usewith the system of the present invention, in which FIG. 2B correspondsto detail region 2B of FIG. 2A.

FIGS. 3A and 3B are, respectively, side and perspective views,respectively, of first and second embodiments of bladder catheterssuitable for use with the ascites treatment system of the presentinvention.

FIG. 4 is a schematic diagram of the electronic components of anexemplary embodiment of the implantable device of the present invention.

FIGS. 5A and 5B are, respectively, a perspective view of the implantabledevice of the present invention with the housing shown in outline and aperspective view of the obverse side of the implantable device with thehousing and low water permeable filler removed.

FIGS. 6A, 6B, 6C and 6D are, respectively, an exploded perspective viewof the drive assembly of the implantable device; front and plan views ofthe upper housing; and a perspective view of the manifold of anexemplary embodiment of the implantable device.

FIGS. 7A and 7B are, respectively, a plan view of the gear pump housingof the implantable device of FIG. 5A, and a plan view of a model of thegear pump constructed in accordance with the principles of the presentinvention.

FIGS. 8A and 8B are, respectively, perspective and top views of thehandpiece portion of an exemplary charging and communication system ofthe present invention;

FIG. 9 is a schematic diagram of the electronic components of anexemplary embodiment of the charging and communication system of thepresent invention.

FIG. 10 is a schematic diagram of the functional components of themonitoring and control software employed in an exemplary embodiment ofthe fluid management system of the present invention.

FIGS. 11-15 are exemplary screenshots illustrating various aspects ofthe user interface of the monitoring and control system of the presentinvention.

VI. DETAILED DESCRIPTION OF THE INVENTION

The fluid management system of the present invention comprises devicesfor facilitating removal of fluid from a body region, such as theperitoneum, pleural cavity or pericardial sac, where drainage isdesired. The devices disclosed herein may be utilized for drainage ofchronic excess fluid accumulation from one body cavity to a second bodycavity, preferably the urinary bladder. Such excess fluid may accumulatedue to an underlying condition, such as cancer. In accordance with theprinciples of the present invention, the fluid management system may beoptimized for use in treating chronic ascites and pleural or pericardialeffusion in patients with cancer, while simultaneously permittingnoninvasive monitoring of cancerous cells. After the fluid managementsystem moves excess fluid containing cancerous cells from the first bodycavity to the bladder and the fluid is excreted during urination, thecancerous cells may be analyzed to, for example, assess the progress ofa cancer treatment or the cancer itself.

System Overview

Referring to FIG. 1, an overview of fluid management system 10 of thepresent invention and analysis station 45 of the present invention areprovided. In FIG. 1, components of the system are not depicted to scaleon either a relative or absolute basis. Fluid management system 10comprises implantable device 20, external charging and communicationsystem 30, and a software-based monitoring and control system 40. In theillustrated embodiment, monitoring and control system 40 is installedand run on a conventional laptop computer used by the patient'sphysician. During patient visits, charging and communication system 30may be coupled, either wirelessly or using a cable, to monitoring andcontrol system 40 to download for review data stored on implantabledevice 20, or to adjust the operational parameters of the implantabledevice. Monitoring and control system 40 also may be configured toupload and store date retrieved from charging and communication system30 to a remote server for later access by the physician or charging andcommunications system 30.

Implantable device 20 comprises an electromechanical pump having housing21 configured for subcutaneous implantation. As described in furtherdetail below, in an embodiment suitable for treating ascites andevacuating cancerous cells to permit noninvasive monitoring of suchcells, implantable device 20 includes an electrically-driven mechanicalgear pump having inlet port 22 coupled to peritoneal catheter 23 andoutlet port 24 coupled to bladder catheter 25. Peritoneal catheter 23comprises a tube having a first end configured to be coupled to pumpinlet 23 and a second end configured to be positioned in the peritonealcavity. In a patient having ascites arising from cancer, the bodygenerates an accumulation of fluid comprising cancerous cells in theperitoneal cavity. Bladder catheter 25 comprises a tube having a firstend configured to be coupled to pump outlet 24 and a second endconfigured to be inserted through the wall of, and fixed within, apatient's bladder. In a preferred embodiment, both catheters are made ofmedical-grade silicone and include polyester cuffs at their distal ends(not shown) to maintain the catheters in position. Peritoneal catheter23 and bladder catheter 25 are coupled to pump housing 21 usingconnector 26 configured to reduce the risk of improper installation andinadvertent disconnection, and may in addition include distinctcross-sections that reduce the risk of improper installation.

Implantable device 20 preferably is configured to move fluid in short(e.g., 10 second) intervals (e.g., every 10-20 minutes). Such short butfrequent intervals are expected to overcome the clogging issues commonto previously-known ascites shunts, by preventing the accumulation ofmaterial on the interior lumens of catheters 23 and 25, and reducing therisk for tissue ingrowth. For ascites treatment, the fluid circuit ofimplantable device 20 preferably is configured to provide an averageflow rate of about 60 ml/hour, although much higher and lower flow ratesare possible if needed. As described in detail below, the pumping timeand volume, including maximum and minimum limits for daily pumpedvolume, may be programmed by the physician using monitoring and controlsystem 40 as required for a specific patient. As further describedbelow, the fluid circuit of implantable device 20 includes pressuresensors that monitor pressure in both the peritoneal cavity and thebladder, such that pumping of fluid into the bladder is disabled untilthe bladder is determined to have sufficient space to accommodateadditional fluid. For patient comfort, implantable device 10 normally isprogrammed not to pump at night or when an accelerometer included in theimplantable device indicates that the patient is asleep (and thusunlikely to be able to void the bladder). Implantable device 20preferably includes multiple separate fail-safe mechanisms, to ensurethat urine cannot pass from the bladder to the peritoneal cavity throughthe pump, thereby reducing the risk of transmitting infection.

Still referring to FIG. 1, external charging and communication system 30in a preferred form comprises base 31 and handpiece 32. In thisembodiment, handpiece 32 contains a controller, a radio transceiver, aninductive charging circuit, a battery, a quality-of-charging indicatorand a display, and is removably coupled to base 31 to recharge itsbattery. Base 31 may contain a transformer and circuitry for convertingconventional 120V power service to a suitable DC current to chargehandpiece 32 when coupled to base 31. In alternative embodiments,handpiece 32 may include such circuitry and a detachable power cord,thereby permitting the handpiece to be directly plugged into aconvention 120V wall socket to charge the battery. In a preferredembodiment, each of implantable device 20 and handpiece 32 includes adevice identifier stored in memory, such that handpiece 32 provided tothe patient is coded to operate only with that patient's specificimplantable device 20.

Handpiece 32 preferably includes housing 33 having multi-function button34, display 35, a plurality of light emitting diodes (LEDs, not shown)and inductive coil portion 36. Multi-function button 34 provides thepatient the ability to issue a limited number of commands to implantabledevice 20, while display 35 provides visible confirmation that a desiredcommand has been input; it also displays battery status. Inductive coilportion 36 houses an inductive coil that is used to transfer energy fromhandpiece 32 to recharge the battery of implantable device 20. The LEDs,which are visible through the material of housing 33 when lit, may bearranged in three rows of two LEDs each, and are coupled to the controlcircuitry and inductive charging circuit contained within handpiece 32.As described in further detail below, the LEDs may be arranged to lightup to reflect the degree of inductive coupling achieved betweenhandpiece 32 and implantable device 20 during recharging of the latter.Alternatively, the LEDs may be omitted and an analog display provided ondisplay 35 indicating the quality of inductive coupling.

As further described in detail below, the control circuitry containedwithin handpiece 32 is coupled to the inductive charging circuit,battery, LEDs and radio transceiver, and includes memory for storinginformation from implantable device 20. Handpiece 32 also preferablyincludes a data port, such as a USB port, that permits the handpiece tobe coupled to monitoring and control system 40 during visits by thepatient to the physician's office. Alternatively, handpiece 32 mayinclude a wireless chip, e.g., conforming to the Bluetooth or IEEE802.11 wireless standards, thereby enabling the handpiece to communicatewirelessly with monitoring and control system 40.

Monitoring and control system 40 is intended primarily for use by thephysician and comprises software configured to run on a conventionallaptop computer. The software enables the physician to configure,monitor and control operation of charging and communication system 30and implantable device 20. As described in detail below, the softwaremay include routines for configuring and controlling pump operation,such as a target amount of fluid to move daily or per motor actuation,intervals between pump actuation, and limits on peritoneal cavitypressure, bladder pressure, pump pressure, and battery temperature.System 40 also may provide instructions to implantable device 20 viacharging and control system 30 to control operation of implantabledevice 20 so as not to move fluid during specific periods (e.g., atnight) or to defer pump actuation if the patient is asleep. System 40further may be configured, for example, to send immediate commands tothe implantable device to start or stop the pump, or to operate the pumpin reverse or at high power to unblock the pump or associated catheters.The software of system 40 also may be configured to download real-timedata relating to pump operation, as well as event logs stored duringoperation of implantable device 20. Based on the downloaded data, e.g.,based on measurements made of the patient's temperature, respiratoryrate, and/or fluid viscosity, the software of system 40 optionally maybe configured to alert the physician to a prediction or detection ofinfection. Finally, system 40 optionally may be configured to remotelyreceive raw or filtered operational data from a patient's handpiece 32over a secure Internet channel.

Ascites, pleural effusion, or pericardial effusion may arise from cancersuch as lung cancer, breast cancer, cancer that has metastasized to thepericardium, ovarian cancer, pancreatic cancer, uterine cancer, cancerof the bowels including colon cancer, melanoma, leukemia, or lymphoma,or from cancer treatment. In such a case, cancerous cells will bepresent in the excess fluid accumulated in the peritoneal cavity,pleural cavity, or pericardial cavity resulting from ascites, pleuraleffusion, or pericardial effusion, respectively.

Advantageously, fluid management system 10 of the present inventionpermits noninvasive monitoring of cancerous cells pumped from a bodycavity to the bladder and excreted during urination. Such an approachenables a patient to comfortably provide cancerous cells for analysiswithout the need of an invasive procedure, such as a tissue biopsy.Applicant has discovered that pH levels in the bladder create anenvironment that neutralizes cancerous cells; thereby obviating concernsthat delivery of cancerous cells to the bladder could cause bladdercancer.

Analysis station 45 is configured to analyze cancerous cells excretedfrom the patient during urination using techniques known in the art ofcancer cell analysis. Analysis station 45 receives a urination samplecontaining fluid comprising cancerous cells that was pumped from a firstbody cavity to the bladder via implantable device 20. Analysis station45 may display the analysis results to a user for review or may becoupled to a computer configured to receive analysis data containing theresults for display. Analysis station 45 may include communicationscircuitry configured to wirelessly, or using a cable, transfer analysisdata to such a computer, and/or to the computer running monitoring andcontrol system 40 for physician review. Analysis station 45 may belocated in close proximity to system 40, e.g., in the same office orhospital, or may be located remotely. As an added benefit, a treatingphysician may review operation of implantable device 20 and obtain aurine sample for analysis of cancerous cells during a single patientvisit. In an embodiment where the analysis station is located in closeproximity to system 40, the cancerous cells may be analyzed moreexpeditiously than conventional methods, in which a tissue biopsy istypically shipped to a remote laboratory for analysis.

Inflow and Outflow Catheters

Referring to FIGS. 2A and 2B, exemplary inflow catheter 50 constructedin accordance with the principles of the present invention is described.Inflow catheter 50 may be configured for use in the peritoneal cavity(and thus correspond to peritoneal catheter 23 of FIG. 1) or pleural orpericardial cavity, and preferably comprises tube 51 of medical-gradesilicone including inlet end 52 having a plurality of through-wall holes53 and outlet end 54. When configured for placement in the peritonealcavity, inflow catheter preferably has length L1 of about 40 cm, withholes 53 extending over length L2 of about 24 cm from inlet end 52.Holes 53 preferably are arranged circumferentially offset by about 90°and longitudinally offset between about 8 mm to 10 mm, as shown in FIG.2B. In one preferred embodiment, 29 holes 53 are arranged in four rowsof 7 holes each, extend only through one wall of the inflow catheter ateach location, and have a size of between 2.0 to 2.5 mm. Inflow catheter50 preferably includes solid silicone plug 55 that fills distal end ofthe lumen for a distance of about 7-10 mm to reduce tissue ingrowth, andradiopaque strip 56 disposed on, or embedded within, the catheter thatextends the entire length of the catheter, that renders the cathetervisible in fluoroscopic or X-ray images. Inflow catheter 50 may alsoinclude a polyester cuff in the region away from holes 53, to promoteadhesion of the catheter to the surrounding tissue, thereby anchoring itin place.

Alternatively, inlet end 52 of inflow catheter 50 may have a spiralconfiguration, and an atraumatic tip, with holes 53 distributed over alength of the tubing to reduce the risk of clogging. As a furtheralternative, inlet end 52 may include a portion having an enlargeddiameter, as disclosed in U.S. Pat. No. 4,657,530, or a reservoir asdisclosed in FIGS. 9 to 16 of U.S. Patent Application Publication US2009/0318844, the entire contents of both of which are incorporatedherein by reference, to further reduce the risk of clogging. Inlet end52 also may terminate in a duck-bill valve, as shown for example in U.S.Pat. No. 4,240,434, thereby permitting the catheter to be cleaned insitu by disconnecting the outlet end of the catheter from implantabledevice 20 and extending a rod from the outlet end of catheter 50 throughthe duckbill valve at the inlet end.

Inlet end 52 also may include a polyester cuff to promote adhesion ofthe catheter to an adjacent tissue wall, thereby ensuring that the inletend of the catheter remains in position. Outlet end 54 also may includea connector for securing the outlet end of the inflow catheter toimplantable device 20. In one preferred embodiment, the distal end ofthe inflow catheter, up to the ingrowth cuff, may be configured to passthrough a conventional 16 F peel-away sheath. In addition, the length ofthe inflow catheter may be selected to ensure that it lies along thebottom of the body cavity, and is sufficiently resistant to torsionalmotion so as not to become twisted or kinked during or afterimplantation.

In one embodiment, inflow catheter 50 may be shaped, e.g., Y-shaped, toinclude a plurality of inflow segments to permit inflow from more thanone body cavity. For example, an inlet end of one segment may bepositioned in the peritoneal cavity and the inlet end of another segmentmay be positioned in the pleural cavity or the pericardial cavity. In analternative embodiment, more than one inflow catheter may be coupled toimplantable device 20 to permit inflow from more than one body cavity.For example, an inlet end of a first inflow catheter may be positionedin the peritoneal cavity and an inlet end of second inflow catheter maybe positioned in the pleural cavity or the pericardial cavity. One ormore valves may be coupled to the multi-inlet catheter, or the multipleinflow catheters, such that fluid may be pumped from exclusively onecavity or from more than one cavity responsive to commands transmittedby the processor of implantable device 20 to the valve(s).

With respect to FIG. 3A, a first embodiment of outflow catheter 60 ofthe present invention is described, corresponding to bladder catheter 25of FIG. 1. Outflow catheter 60 preferably comprises tube 61 ofmedical-grade silicone having inlet end 62 and outlet end 63 includingspiral structure 64, and polyester ingrowth cuff 65. Outflow catheter 60includes a single internal lumen that extends from inlet end 62 to asingle outlet at the tip of spiral structure 64, commonly referred to asa “pigtail” design. Inlet end 62 may include a connector for securingthe inlet end of the outflow catheter to implantable device 20, or mayhave a length that can be trimmed to fit a particular patient.

When configured for use as the outflow catheter in an ascites treatmentsystem, outflow catheter may have length L3 of about 45 cm, with cuff 65placed length L4 of about 5 to 6 cm from spiral structure 64. Outflowcatheter 60 may be loaded onto a stylet with spiral structure 64straightened, and implanted using a minimally invasive technique inwhich outlet end 63 and spiral structure 64 are passed through the wallof a patient's bladder using the stylet. When the stylet is removed,spiral structure 64 returns to the coiled shape shown in FIG. 3A. Onceoutlet end 63 of outflow catheter 60 is disposed within the patient'sbladder, the remainder of the catheter is implanted using a tunnelingtechnique, such that inlet end 62 of the catheter may be coupled toimplantable device 20. Spiral structure 64 may reduce the risk thatoutlet end 63 accidentally will be pulled out of the bladder before thetissue surrounding the bladder heals sufficiently to incorporateingrowth cuff 65, thereby anchoring the outflow catheter in place.

In a preferred embodiment, the outflow catheter is configured to passthrough a conventional peel-away sheath. Outflow catheter 60 preferablyis sufficiently resistant to torsional motion so as not to becometwisted or kinked during or after implantation. In a preferredembodiment, inflow catheter 50 and outflow catheter 60 preferably aredifferent colors, have different exterior shapes (e.g., square andround) or have different connection characteristics so that they cannotbe inadvertently interchanged during connection to implantable device20. Optionally, outflow catheter 60 may include an internal duckbillvalve positioned midway between inlet 62 and outlet end 63 of thecatheter to insure that urine does not flow from the bladder into theperitoneal cavity if the outflow catheter is accidentally pulled freefrom the pump outlet of implantable device 20.

In an alternative embodiment, the inflow and outflow catheters devicesmay incorporate one or several anti-infective agents to inhibit thespread of infection between body cavities. Examples of anti-infectiveagents which may be utilized may include, e.g., bacteriostaticmaterials, bacteriocidal materials, one or more antibiotic dispensers,antibiotic eluting materials, and coatings that prevent bacterialadhesion, and combinations thereof.

Alternatively, rather than comprising separate catheters, inflow andoutflow catheters may share a common wall. This arrangement may beutilized ideally for an ascites treatment embodiment because the bladderand peritoneal cavity share a common wall, thereby facilitatinginsertion of a single dual-lumen tube. In addition, either or both ofthe inflow or outflow catheters may be reinforced along a portion of itslength or along its entire length using ribbon or wire braiding orlengths of wire or ribbon embedded or integrated within or along thecatheters. The braiding or wire may be fabricated from metals such asstainless steels, superelastic metals such as nitinol, or from a varietyof suitable polymers.

With respect to FIG. 3B, a second embodiment of an outflow catheter ofthe present invention is described, in which similar components areidentified with like-primed numbers. Outflow catheter 60′ preferablycomprises tube 61′ of medical-grade silicone having inlet end 62′,outlet end 63′ and polyester ingrowth cuff 65′. In accordance with thisembodiment, outlet end 63′ includes malecot structure 66, illustrativelycomprising four resilient wings 67 that expand laterally away from theaxis of the catheter to reduce the risk that outlet end 63′ of thecatheter will be inadvertently pulled loose after placement. Inlet end62′ may include a connector for securing the inlet end of the outflowcatheter to implantable device 20, or may have a length that can betrimmed to fit a particular patient.

Malecot structure 66 preferably is constructed so that wings 67 deformto a substantially flattened configuration when a stylet is insertedthrough the lumen of the catheter. In this manner, outflow catheter 60′may be loaded onto a stylet, and using a minimally invasive technique,outlet end 63′ and malecot structure 66 may be passed through the wallof a patient's bladder using the stylet. When the stylet is removed,wings 67 of the malecot structure return to the expanded shape shown inFIG. 3B. Once outlet end 63′ of outflow catheter 60′ is coupled to thepatient's bladder, the remainder of the catheter is implanted using atunneling technique, such that inlet end 62′ of the catheter may becoupled to implantable device 20. Malecot structure 66 may reduce therisk that outlet end 63′ accidentally will be pulled out of the bladderbefore the tissue surrounding the bladder heals sufficiently toincorporate ingrowth cuff 65′. As for the embodiment of FIG. 3A, theoutflow catheter of FIG. 3B may be configured to pass through aconventional peel-away sheath, and preferably is sufficiently resistantto torsional motion so as not to become twisted or kinked during orafter implantation.

As mentioned above, for ascites treatment systems, the outlet end of theoutflow catheter preferably is configured for placement in the urinarybladder, and this configuration also may be employed for pleuraleffusion and pericardial effusion treatment systems. Alternatively, theoutflow catheter used for systems designed for treatment of pleural orpericardial effusions may be configured so that the outlet end isdisposed in the peritoneal cavity, such that effusive fluid drained intothe peritoneal cavity is reabsorbed and excreted, e.g., through thekidneys. For such embodiments, outflow catheter 60 may be constructedsimilar to inflow catheter 50 of FIGS. 2, and may have a plurality ofholes to drain fluid into the peritoneal cavity. For treatment ofascites, pleural effusion, and/or pericardial effusion arising fromcancer, the outlet end of the outflow catheter preferably is configuredfor placement in the urinary bladder such that cancerous cells areneutralized by pH levels in the bladder, excreted during urination, andanalyzed in a noninvasive manner.

The Implantable Device

Referring now to FIG. 4, a schematic depicting the functional blocks ofimplantable device 20 of the present invention is described. Implantabledevice 20 includes control circuitry, illustratively processor 70coupled to nonvolatile memory 71, such as flash memory or electricallyerasable programmable read only memory, and volatile memory 72 via databuses. Processor 70 is electrically coupled to electric motor 73,battery 74, inductive circuit 75, radio transceiver 76 and a pluralityof sensors, including humidity sensor 77, a plurality of temperaturesensors 78, accelerometer 79, a plurality of pressure sensors 80, andrespiratory rate sensor 81. Inductive circuit 75 is electrically coupledto coil 84 to receive energy transmitted from charging and communicationsystem 30, while transceiver 76 is coupled to antenna 82, and likewiseis configured to communicate with a transceiver in charging andcommunication system 30, as described below. Optionally, inductivecircuit 75 also may be coupled to infrared light emitting diode 83.Motor 73 may include a dedicated controller, which interprets andactuates motor 73 responsive to commands from processor 70. All of thecomponents depicted in FIG. 4 are contained within a low volume sealedbiocompatible housing, as shown in FIG. 5A.

Processor 70 executes firmware stored in nonvolatile memory 71 whichcontrols operation of motor 73 responsive to signals generated by motor73, sensors 77-81 and commands received from transceiver 76. Processor70 also controls reception and transmission of messages via transceiver76 and operation of inductive circuit 75 to charge battery 74. Inaddition, processor 70 receives signals generated by Hall Effect sensorslocated within motor 73, which are used to compute direction andrevolutions of the gears of the gear pump, and thus fluid volume pumpedand the viscosity of that fluid, as described below. Processor 70preferably includes a low-power mode of operation and includes aninternal clock, such that the processor can be periodically awakened tohandle pumping, pump tick mode, or communications and chargingfunctions, and/or awakened to handle commands received by transceiver 76from handpiece 32. In one embodiment, processor 70 comprises a member ofthe MSP430 family of microcontroller units available from TexasInstruments, Incorporated, Dallas, Tex., and may incorporate thenonvolatile memory, volatile memory, and radio transceiver componentsdepicted in FIG. 4. In addition, the firmware executed on processor 70may be configured to respond directly to commands sent to implantabledevice 20 via charging and communication system 30. Processor 70 also isconfigured to monitor operation of motor 72 (and any associated motorcontroller) and sensors 78-81, as described below, and to store datareflecting operation of the implantable device, including event logs andalarms. Thus, data is reported to the charging and communication systemwhen it is next wirelessly coupled to the implantable device. In apreferred embodiment, processor 70 generates up to eighty log entriesper second prior to activating the pump, about eight log entries persecond when the implantable system is actively pumping and about one logentry per hour when not pumping.

Nonvolatile memory 71 preferably comprises flash memory or EEPROM, andstores a unique device identifier for implantable device 20, firmware tobe executed on processor 70, configuration set point data relating tooperation of the implantable device, and optionally, coding to beexecuted on transceiver 76 and/or inductive circuit 75, and a separatemotor controller, if present. Firmware and set point data stored onnonvolatile memory 71 may be updated using new instructions provided bycontrol and monitoring system 40 via charging and communication system30. Volatile memory 72 is coupled to and supports operation of processor70, and stores data and event log information gathered during operationof implantable device 20. Volatile memory 72 also serves as a buffer forcommunications sent to, and received from, charging and communicationsystem 30.

Transceiver 76 preferably comprises a radio frequency transceiver and isconfigured for bi-directional communications via antenna 76 with asimilar transceiver circuit disposed in handpiece 32 of charging andcommunication system 30. Transceiver 76 also may include a low powermode of operation, such that it periodically awakens to listen forincoming messages and responds only to those messages including theunique device identifier assigned to that implantable device.Alternatively, because transceiver 76 communicates only with thecorresponding transceiver in handpiece 32 of its associated charging andcommunication system 30, transceiver 76 may be configured to send orreceive data only when inductive circuit 75 of the implantable device isactive. In addition, transceiver 76 may employ an encryption routine toensure that messages sent from, or received by, the implantable devicecannot be intercepted or forged.

Inductive circuit 75 is coupled to coil 84, and is configured torecharge battery 74 of the implantable device when exposed to a magneticfield supplied by a corresponding inductive circuit within handpiece 32of charging and communication system 30. In one embodiment, inductivecircuit 75 is coupled to optional infrared LED 83 that emits an infraredsignal when inductive circuit 75 is active. The infrared signal may bereceived by handpiece 32 of charging and communication system 30 toassist in locating the handpiece relative to the implantable device,thereby improving the magnetic coupling and energy transmission to theimplantable device.

In accordance with one aspect of the present invention, inductivecircuit 75 optionally may be configured not only to recharge battery 74,but to directly provide energy to motor 73 in a “boost” mode orjog/shake mode to unblock the pump. In particular, if processor 70detects that motor 73 is stalled, e.g., due to a block created by theproteinaceous ascitic fluid, an alarm may be stored in memory. Whenimplantable device 20 next communicates with charging and communicationsystem 30, the alarm is reported to handpiece 32, and the patient may begiven the option of depressing multifunction button 34 to apply anovervoltage to motor 73 from inductive circuit 75 for a predeterminedtime period to free the pump blockage. Alternatively, depressing themulti-function button may cause processor 70 to execute a set ofcommands by which motor 73 is jogged or shaken, e.g., by alternatinglyrunning the motor is reverse and then forward, to disrupt the blockage.Because such modes of operation may employ higher energy consumptionthan expected during normal operation, it is advantageous to drive themotor during such procedures with energy supplied via inductive circuit75.

Battery 74 preferably comprises a lithium ion or lithium polymer batterycapable of long lasting operation, e.g., up to three years, whenimplanted in a human, so as to minimize the need for re-operations toreplace implantable device 20. In one preferred embodiment, battery 74supplies a nominal voltage of 3.6V, a capacity of 150 mAh when new, anda capacity of about 120 mAh after two years of use. Preferably, battery74 is configured to supply a current of 280 mA to motor 73 when pumping;25 mA when the transceiver is communicating with charging andcommunication system 30; 8 mA when processor 70 and related circuitry isactive, but not pumping or communicating; and 0.3 mA when theimplantable device is in low power mode. More preferably, battery 74should be sized to permit a minimum current of at least 450 mAh for aperiod of 10 seconds and 1 A for 25 milliseconds during each chargingcycle.

Motor 73 preferably is a brushless direct current or electronicallycommuted motor having a splined output shaft that drives a set offloating gears that operate as a gear pump, as described below. Motor 73may include a dedicated motor controller, separate from processor 70,for controlling operation of the motor. Motor 73 may include a pluralityof Hall Effect sensors, preferably two or more, for determining motorposition and direction of rotation. Due to the high humidity that may beencountered in implantable device 20, processor 70 may includeprogramming to operate motor 73, although with reduced accuracy, even ifsome or all of the Hall Effect sensors fail.

In a preferred embodiment, motor 73 is capable of driving the gear pumpto generate a nominal flow rate of 150 ml/min and applying a torque ofabout 1 mNm against a pressure head of 30 cm water at 3000 RPM. In thisembodiment, the motor preferably is selected to drive the gears at from1000 to 5000 RPM, corresponding to flow rates of from 50 to 260 ml/min,respectively. The motor preferably has a stall torque of at least 3 mNmat 500 mA at 3 V, and more preferably 6 mNm in order to crush non-solidascitic proteinaceous materials. As discussed above, the motorpreferably also supports a boost mode of operation, e.g., at 5 V, whenpowered directly through inductive circuit 75. Motor 73 preferably alsois capable of being driven in reverse as part of a jogging or shakingprocedure to unblock the gear pump.

In accordance with one aspect of the present invention, processor 70 maybe programmed to automatically and periodically wake up and enter a pumptick mode. In this mode of operation, the gear pump is advancedslightly, e.g., about 120° as measured by the Hall Effect sensors,before processor 70 returns to low power mode. Preferably, this intervalis about every 20 minutes, although it may be adjusted by the physicianusing the monitoring and control system. This pump tick mode is expectedto prevent the ascitic fluid, which has a high protein content, frompartially solidifying, and blocking the gear pump, and is expected to beespecially advantageous in overcoming the problem of clogging observedin previously-known implantable systems designed to treat chronicascites.

In addition, processor 70 also may be programmed to enter a jog or shakemode when operating on battery power alone, to unblock the gear pump.Similar to the boost mode available when charging the implantable devicewith the handpiece of charging and communication system 30, the jog orshake mode causes the motor to rapidly alternate the gears betweenforward and reverse directions to crush or loosen and proteinaceousbuildup in the gear pump or elsewhere in the fluid path. Specifically,in this mode of operation, if the motor does not start to turn within acertain time period after it is energized (e.g. 1 second), the directionof the motion is reversed for a short period of time and then reversedagain to let the motor turn in the desired direction. If the motor doesstill not turn (e.g., because the gear pump is jammed) the direction isagain reversed for a period of time (e.g., another 10 msec). If themotor still is not able to advance the time interval between reversalsof the motor direction is reduced to allow for the motor to develop morepower, resulting in a shaking motion of the gears. If the motor does notturn forward for more than 4 seconds, the jog mode of operation isstopped, and an alarm is written to the event log. If the motor wasunable to turn forward, processor 70 will introduce a backwards tickbefore the next scheduled fluid movement. A backward tick is the same asa tick (e.g., about 120° forward movement of the motor shaft) but in thereverse direction, and is intended to force the motor backwards beforeturning forward, which should allow the motor to gain momentum.

Sensors 77-81 continually monitor humidity, temperature, acceleration,pressure, and respiratory rate, and provide corresponding signals toprocessor 70. In particular, humidity sensor 77 is arranged to measurehumidity within the housing of the implantable device, to ensure thatthe components of implantable device are operated within expectedoperational limits. Humidity sensor 77 preferably is capable of sensingand reporting humidity within a range or 20% to 100% with high accuracy.One or more of temperature sensors 78 may be disposed within the housingand monitor the temperature of the implantable device, and in particularbattery 74 to ensure that the battery does not overheat during charging,while another one or more of temperature sensors 78 may be disposed soas to contact fluid entering at inlet 62 and thus monitor thetemperature of the fluid, e.g., for use in predicting or detectinginfection on the basis of an increase in the fluid's temperature.Accelerometer 79 is arranged to measure acceleration of the implant,preferably along at least two axes, to detect periods of inactivity,e.g., to determine whether the patient is sleeping. This information isprovided to processor 70 to ensure that the pump is not operated whenthe patient is indisposed to attend to voiding of the bladder.

Implantable device 20 preferably includes multiple pressure sensors 80,which are continually monitored during waking periods of the processor.As described below with respect to FIG. 6A, the implantable device ofthe present invention preferably includes four pressure sensors: asensor to measure the pressure in the source cavity (e.g., peritoneal,pleural or pericardial cavity), a sensor to measure the ambientpressure, a sensor to measure the pressure at the outlet of the gearpump, and a sensor to measure the pressure in the sink cavity (e.g.,bladder, or for pleural or pericardial systems, the peritoneal cavity).These sensors preferably are configured to measure absolute pressurebetween 450 mBar and 1300 mBar while consuming less than 50 mW at 3V.Preferably, the sensors that measure pressure at the pump outlet and inthe sink are placed across a duckbill valve, which prevents reverse flowinto the gear pump and also permits computation of flow rate based onthe pressure drop across the duckbill valve. In an embodiment withmultiple inlet ends disposed in multiple source cavities, theimplantable device of the present invention preferably includes anadditional sensor to measure the pressure in each additional sourcecavity (e.g., peritoneal, pleural or pericardial cavity).

Respiratory rate monitor 81 is configured to measure the patient'srespiratory rate, e.g., for use in predicting or detecting infectionbased on an increase in the patient's respiratory rate. Alternatively,the patient's respiratory rate may be measured based on the outputs ofone or more of pressure sensors 80, e.g., based on changes in theambient pressure or the pressure in the source cavity (e.g., peritoneal,plural, or pericardial cavity) caused by the diaphragm periodicallycompressing that cavity during breathing.

In a preferred embodiment, processor 70 is programmed to pump fluid fromthe source cavity to the sink cavity only when the pressure in thesource cavity exceeds a first predetermined value, and the pressure inthe sink cavity is less than a second predetermined value. In anembodiment with multiple inlet ends disposed in multiple sourcecavities, processor 70 is programmed to pump fluid from the first sourcecavity, second source cavity, or both to the sink cavity only when thepressure in the first source cavity, second source cavity, or both,respectively, exceed a first predetermined value, a second predeterminedvalue, or both the first and second predetermined values, respectively,and the pressure in the sink cavity is less than a third predeterminedvalue. To account for patient travel from a location at sea level to ahigher altitude, the ambient pressure measurement may be used tocalculate a differential value for the peritoneal pressure. In this way,the predetermined pressure at which the pump begins operation may bereduced, to account for lower atmospheric pressure. Likewise, theambient pressure may be used to adjust the predetermined value forbladder pressure. In this way, the threshold pressure at which thepumping ceases may be reduced, because the patient may experiencebladder discomfort at a lower pressure when at a high altitude location.

Referring now to FIGS. 5A and 5B, further details of an exemplaryembodiment of implantable device 90 are provided. In FIG. 5A, housing 91is shown as transparent, although it should of course be understood thathousing 91 comprises opaque biocompatible plastic and/or metal alloymaterials. In FIG. 5B, the implantable device is shown with lowerportion 92 of housing 91 removed from upper housing 93 and without aglass bead/epoxy filler material that is used to prevent moisture fromaccumulating in the device. In FIGS. 5A and 5B, motor 94 is coupled togear pump housing 95, which is described in greater detail with respectto FIGS. 6 and 7. The electronic components discussed above with respectto FIG. 4 are disposed on flexible circuit board substrate 96, whichextends around and is fastened to support member 97. Coil 98(corresponding to coil 84 of FIG. 4) is disposed on flap 99 of thesubstrate and is coupled to the electronic components on flap 100 byflexible cable portion 101. Support member 97 is fastened to upperhousing 93 and provides a cavity that holds battery 102 (correspondingto battery 74 of FIG. 4). Lower portion 92 of housing 91 includes port103 for injecting the glass bead/epoxy mixture after upper portion 93and lower portion 92 of housing 91 are fastened together, to reducespace in the housing in which moisture can accumulate.

Housing 91 also may include features designed to reduce movement of theimplantable pump once implanted within a patient, such as a suture holeto securely anchor the implantable device to the surrounding tissue.Housing 91 may in addition include a polyester ingrowth patch thatfacilitates attachment of the implantable device to the surroundingtissue following subcutaneous implantation.

Additionally, the implantable device optionally may incorporateanti-clogging agents, such enzyme eluting materials that specificallytarget the proteinaceous components of ascites, enzyme eluting materialsthat specifically target the proteinaceous and encrustation promotingcomponents of urine, chemical eluting surfaces, coatings that preventadhesion of proteinaceous compounds, and combinations thereof. Suchagents, if provided, may be integrated within or coated upon thesurfaces of the various components of the system.

Referring now to FIGS. 6A to 6D, further details of the gear pump andfluid path are described. In FIGS. 6A-6D, like components are identifiedusing the same reference numbers from FIGS. 5A and 5B. FIG. 6A is anexploded view showing assembly of motor 94 with gear pump housing 95 andupper housing 93, as well as the components of the fluid path within theimplantable device. Upper housing 93 preferably comprises a highstrength plastic or metal alloy material that can be molded or machinedto include openings and channels to accommodate inlet nipple 102, outletnipple 103, pressure sensors 104 a-104 d, manifold 105 and screws 106.Nipples 102 and 103 preferably are machined from a high strengthbiocompatible metal alloy, and outlet nipple 103 further includeschannel 107 that accepts elastomeric duckbill valve 108. Outlet nipple103 further includes lateral recess 109 that accepts pressure sensor 104a, which is arranged to measure pressure at the inlet end of the outflowcatheter, corresponding to pressure in the patient's bladder (orperitoneal cavity).

Referring now also to FIGS. 6B and 6C, inlet nipple 102 is disposedwithin opening 110, which forms a channel in upper housing 93 thatincludes opening 111 for pressure sensor 104 b and opening 112 thatcouples to manifold 105. Pressure sensor 104 b is arranged to measurethe pressure at the outlet end of the inflow catheter, corresponding topressure in the peritoneal (or pleural or pericardial) cavity. Outletnipple 103, including duckbill valve 107, is disposed within opening 113of upper housing 93 so that lateral recess 108 is aligned with opening114 to permit access to the electrical contacts of pressure sensor 104a. Opening 113 forms channel 115 that includes opening 116 for pressuresensor 104 c, and opening 117 that couples to manifold 105. Upperhousing 93 preferably further includes opening 118 that forms a channelincluding opening 119 for accepting pressure sensor 104 d. Pressuresensor 104 d measures ambient pressure, and the output of this sensor isused to calculate differential pressures as described above. Upperhousing further includes notch 120 for accepting connector 26 (seeFIG. 1) for retaining the inflow and outflow catheters coupled to inletand outlet nipples 102 and 103. Upper housing 93 further includes recess121 to accept manifold 105, and peg 122, to which support member 97 (seeFIG. 5B) is connected.

As shown in FIGS. 6A and 6D, manifold 105 preferably comprises a moldedelastomeric component having two separate fluid channels that coupleinlet and outlet flow paths through upper housing 93 to the gear pump.The first channel includes inlet 124 and outlet 125, while the secondchannel includes inlet 126 and outlet 127. Inlet 124 couples to opening112 (see FIG. 6C) of the inflow path and outlet 127 couples to opening117 of the outflow path. Manifold 105 is configured to improvemanufacturability of the implantable device, by simplifying constructionof upper housing 93 and obviating the need to either cast or machinecomponents with complicated non-linear flow paths.

Referring now to FIGS. 6A, 7A and 7B, motor 94 is coupled to gear pumphousing 95 using mating threads 130, such that splined shaft 131 ofmotor 94 passes through bearing 132. The gear pump of the presentinvention comprises intermeshing gears 133 and 134 enclosed in gear pumphousing 95 by O-ring seal 135 and plate 136. The gear pump isself-priming. Plate 136 includes openings 137 and 138 that mate withoutlet 125 and inlet 126 of manifold 105, respectively. Splined shaft131 of motor 94 extends into opening 139 of gear 133 to provide floatingengagement with that gear. Interaction of the splined shaft with thegears is described below with respect to FIG. 7B.

FIG. 7A depicts the obverse side of gear pump housing 95 of FIG. 6A, andincludes recess 140 that is sized to accept gears 133 and 134, andgroove 141 that accepts O-ring seal 135. Gears 133 and 134 are seatedwithin recess 140 such that splined shaft 131 extends through opening142 and floats within keyed opening 139 of gear 133. Gears 133 and 134are dimensioned so as to sit within recess 140 with a close tolerance(e.g., 0.2 mm) to wall 143 of the recess, but spin as freely as theviscosity of the fluid permits. Openings 137 and 138 of plate 136 (seeFIG. 6A) are positioned over the juncture of gears 133 and 134 (shown indotted line in FIG. 7A) so that rotation of gear 133 in a clockwisedirection (when viewed from above) creates suction that draws fluid intothe gear pump housing through opening 137, and expels fluid throughopening 138. Likewise, if motor 94 drives gear 133 in a counterclockwisedirection (as viewed from above), the gear pump will draw fluid into thegear pump housing through opening 138 and expel it through opening 137,thereby reversing flow.

As depicted in the simplified model of FIG. 7B, gear 134 has no axle,but instead floats freely within its portion of recess 140. Splinedshaft 131 engages keyed opening 139 of gear 133, so that gear 133 floatson splined shaft 131. Advantageously, this arrangement improves pumpefficiency and manufacturability, and reduces power consumption by motor94 by reducing the effects of manufacturing variations and thermaleffects. In particular, slight variations in motor shaft eccentricity orstraightness, resulting from manufacturing tolerances or differentialthermal expansion, will not cause the gear to bind against the interiorof recess 140 or against gear 134. Instead, different portions of thesurfaces of shaft 131 and keyed opening 139 contact one another duringrevolution of shaft 131 to continuously transmit rotational torque togear 133. However, energy-wasting forces resulting from shafteccentricities, variations in manufacturing tolerances or differentialthermal expansion of the components are reduced. In addition, thisfloating arrangement may reduce the risk that particulate matter causesbinding between the gears and wall 143, since the gears may movelaterally to accommodate such particulate matter.

Gears 133 and 134 include intermeshing lobes 144 that positivelydisplace fluid as they engage and disengage, with substantially nobypass flow. In this manner the volume and viscosity of fluidtransported by gears 133 and 134 may computed by tracking the number ofmotor revolutions sensed by the Hall Effect sensors disposed withinmotor 94. As further shown in FIGS. 7A and 7B, recess 140 of gear pumphousing 95 comprises two interconnected, substantially circular, lobes.This arrangement retains gears 133 and 134 in proper relation to wall143 of the recess, as well as relative to one another. In a preferredembodiment, cusps 145, formed where the two lobes intersect, areconfigured to form tangents to radii drawn from the centers of therespective lobes. Advantageously, configuring the cusps in this mannerreduces the potential for gears 133 and 134 to impinge upon wall 143.

The Charging and Communication System

Referring to FIGS. 8A, 8B and 9, charging and communication system 150of the present invention (corresponding to system 30 of FIG. 1) is nowdescribed in greater detail. In one preferred embodiment, charging andcommunication system 150 comprises handpiece 151 and base 31 (see FIG.1). Base 31 provides comprises a cradle for recharging handpiece 151,and preferably contains a transformer and circuitry for convertingconventional 120V power service to a suitable DC current to chargehandpiece 151 when it is coupled to the base. Alternatively, handpiece151 may include circuitry for charging the handpiece battery, and adetachable power cord. In this embodiment, handpiece 151 may be directlyplugged into a convention 120V wall socket for charging, and the powercord removed when the handpiece is used to recharge the implantabledevice.

As shown in FIG. 9, handpiece 151 contains controller 152,illustratively the processor of a micro-controller unit coupled tononvolatile memory 153 (e.g., either EEPROM or flash memory), volatilememory 154, radio transceiver 155, inductive circuit 156, battery 157,indicator 158 and display 159. Controller 152, memories 153 and 154, andradio transceiver 155 may be incorporated into a single microcontrollerunit, such as the MPS430 family of microprocessors, available from TexasInstruments Incorporated, Dallas, Tex. Transceiver 155 is coupled toantenna 160 for sending and receiving information to implantable device20. Battery 157 is coupled to connector 161 that removably couples witha connector in base 31 to recharge the battery. Port 162, such as a USBport or comparable wireless circuit, is coupled to controller 152 topermit information to be exchanged between handpiece 151 and themonitoring and control system. Inductive circuit 156 is coupled to coil163. Input device 164, preferably a multi-function button, also iscoupled to controller 152 to enable a patient to input a limited numberof commands. Indicator 158 illustratively comprises a plurality of LEDsthat illuminate to indicate the quality of charge coupling achievedbetween the handpiece and implantable device, and therefore assist inoptimizing the positioning of handpiece 151 relative to the implantabledevice during recharging. In one preferred embodiment, indicator 158 isomitted, and instead a bar indicator provided on display 159 thatindicates the quality-of-charging resulting from the coupling of coils163 and 84.

In a preferred embodiment, handpiece 151 includes a device identifierstored in nonvolatile memory 153 that corresponds to the deviceidentifier stored in nonvolatile memory 71 of the implantable device,such that handpiece 151 will communicate only with its correspondingimplantable device 20. Optionally, a configurable handpiece for use in aphysician's office may include the ability to interrogate an implantabledevice to request that device's unique device identifier, and thenchange the device identifier of the monitoring and control system 40 tothat of the patient's implantable device, so as to mimic the patient'shandpiece. In this way, a physician may adjust the configuration of theimplantable device if the patient forgets to bring his handpiece 151with him during a visit to the physician's office.

Controller 152 executes firmware stored in nonvolatile memory 153 thatcontrols communications and charging of the implantable device.Controller 152 also is configured to transfer and store data, such asevent logs, uploaded to handpiece 151 from the implantable device, forlater retransmission to monitoring and control system 40 via port 162,during physician office visits. Alternatively, handpiece 151 may beconfigured to recognize a designated wireless access point within thephysician's office, and to wirelessly communicate with monitoring andcontrol system 40 during office visits. As a further alternative, base31 may include telephone circuitry for automatically dialing anduploading information stored on handpiece 151 to a physician's websitevia a secure connection, such as alarm information.

Controller 152 preferably includes a low-power mode of operation andincludes an internal clock, such that the controller periodicallyawakens to communicate with the implantable device to log data or toperform charging functions. Controller 152 preferably is configured toawaken when placed in proximity to the implantable device to performcommunications and charging functions, and to transmit commands inputusing input device 164. Controller 152 further may includes programmingfor evaluating information received from the implantable device, andgenerating an alarm message on display 159. Controller 152 also mayinclude firmware for transmitting commands input using input device 164to the implantable device, and monitoring operation of the implantabledevice during execution of such commands, for example, during boost orjogging/shaking operation of the gear pump to clear a blockage. Inaddition, controller 152 controls and monitors various power operationsof handpiece 151, including operation of inductive circuit 156 duringrecharging of the implantable device, displaying the state of charge ofbattery 74, and controlling charging and display of state of chargeinformation for battery 157.

Nonvolatile memory 153 preferably comprises flash memory or EEPROM, andstores the unique device identifier for its associated implantabledevice, firmware to be executed by controller 152, configuration setpoint, and optionally, coding to be executed on transceiver 155 and/orinductive circuit 156. Firmware and set point data stored on nonvolatilememory 153 may be updated using information supplied by control andmonitoring system 40 via port 162. Volatile memory 154 is coupled to andsupports operation of controller 152, and stores data and event loginformation uploaded from implantable device 20.

In addition, in a preferred embodiment, nonvolatile memory 153 storesprogramming that enables the charging and communication system toperform some initial start-up functions without communicating with themonitor and control system. In particular, memory 153 may includeroutines that make it possible to test the implantable device duringimplantation using the charging and communication system alone in a“self-prime mode” of operation. In this case, a button may be providedthat allows the physician to manually start the pump, and display 159 isused to provide feedback whether the pumping session was successful ornot. Display 159 of the charging and communication system also may beused to display error messages designed to assist the physician inadjusting the position of the implantable device or inflow or outflowcatheters. These functions preferably are disabled after the initialimplantation of the implantable device.

Transceiver 155 preferably comprises a radio frequency transceiver,e.g., conforming to the Bluetooth or IEEE 802.11 wireless standards, andis configured for bi-directional communications via antenna 160 withtransceiver circuit 76 disposed in the implantable device. Transceiver155 also may include a low power mode of operation, such that itperiodically awakens to listen for incoming messages and responds onlyto those messages including the unique device identifier assigned to itsassociated implantable device. Transceiver 155 preferably employs anencryption routine to ensure that messages sent to, or received from,the implantable device cannot be intercepted or forged.

Inductive circuit 156 is coupled to coil 163, and is configured toinductively couple with coil 84 of the implantable device to rechargebattery 74 of the implantable device. In one embodiment, inductivecircuit 156 is coupled to indicator 158, preferably a plurality of LEDsthat light to indicate the extent of magnetic coupling between coils 163and 84 (and thus quality of charging), thereby assisting in positioninghandpiece 151 relative to the implantable device. In one preferredembodiment, inductive coils 84 and 163 are capable of establishing goodcoupling through a gap of 35 mm, when operating at a frequency of 315kHz or less. In an embodiment in which implantable device includesoptional infrared LED 83, charging and communication system 30 mayinclude an optional infrared sensor (not shown) which detects thatinfrared light emitted by LED 83 and further assists in positioninghandpiece 151 to optimize magnetic coupling between coils 163 and 84,thereby improving the energy transmission to the implantable device.

In accordance with one aspect of the present invention, controller 152may be configured to periodically communicate with the implantabledevice to retrieve temperature data generated by temperature sensor 78and stored in memory 72 during inductive charging of battery 74.Controller 152 may include firmware to analyze the battery temperature,and to adjust the charging power supplied to inductive circuit 163 tomaintain the temperature of the implantable device below a predeterminedthreshold, e.g., less than 2° C. above body temperature. That thresholdmay be set to reduce thermal expansion of the battery and surroundingelectronic and mechanical components, for example, to reduce thermalexpansion of motor and gear pump components and to reduce the thermalstrain applied to the seal between lower portion 92 of housing and upperhousing 93. In a preferred embodiment, power supplied to inductive coil163 is cycled between high power (e.g., 120 mA) and low power (e.g., 40mA) charging intervals responsive to the measured temperature within theimplantable device.

As discussed above with respect to inductive circuit 75 of theimplantable device, inductive circuit 156 optionally may be configuredto transfer additional power to motor 73 of the implantable device, viainductive circuit 75 and battery 74, in a “boost” mode or jogging modeto unblock the gear pump. In particular, if an alarm is transmitted tocontroller 152 that motor 73 is stalled, e.g., due to a block created byascitic fluid, the patient may be given the option of using input device164 to apply an overvoltage to motor 73 from inductive circuit 75 for apredetermined time period to free the blockage. Alternatively,activating input device 164 may cause controller 152 to commandprocessor 70 to execute a routine to jog or shake the gear pump byrapidly operating motor 74 in reverse and forward directions to disruptthe blockage. Because such modes of operation may employ higher energyconsumption than expected during normal operation, inductive circuits156 and 75 may be configured to supply the additional energy for suchmotor operation directly from the energy stored in battery 157, insteadof depleting battery 74 of the implantable device.

Battery 157 preferably comprises a lithium ion or lithium polymerbattery capable of long lasting operation, e.g., up to three years.Battery 157 has sufficient capacity to supply power to handpiece 151 tooperate controller 152, transceiver 155, inductive circuit 156 and theassociated electronics while disconnected from base 31 and duringcharging of the implantable device. In a preferred embodiment, battery157 has sufficient capacity to fully recharge battery 74 of theimplantable device from a depleted state in a period of about 2-4 hours.Battery 157 also should be capable of recharging within about 2-4 hours.It is expected that for daily operation moving 700 ml of fluid, battery157 and inductive circuit 156 should be able to transfer sufficientcharge to battery 74 via inductive circuit 75 to recharge the batterywithin about 30 minutes. Battery capacity preferably is supervised bycontroller 152 using a charge accumulator algorithm.

Referring again to FIGS. 8A and 8B, handpiece 151 preferably includeshousing 165 having multi-function button 166 (corresponding to inputdevice 164 of FIG. 9) and display 167 (corresponding to display 159 ofFIG. 9). Plurality of LEDs 168 is disposed beneath a translucent portionof handpiece 151, and corresponds to indicator 158 of FIG. 9. Port 169enables the handpiece to be coupled to monitoring and control system 40(and corresponds to port 162 of FIG. 9), while connector 170(corresponding to connector 161 in FIG. 9) permits the handpiece to becoupled to base 31 to recharge battery 157. Multi-function button 166provides the patient the ability to input a limited number of commandsto the implantable device. Display 167, preferably an OLED or LCDdisplay, provides visible confirmation that a desired command inputusing multifunction button 166 has been received. Display 167 also maydisplay the status and state of charge of battery 74 of the implantabledevice, the status and state of charge of battery 157 of handpiece 151,signal strength of wireless communications, quality-of-charging, errorand maintenance messages. Inductive coil portion 171 of housing 165houses inductive coil 163.

LEDs 168 are visible through the material of housing 165 when lit, andpreferably are arranged in three rows of two LEDs each. During charging,the LEDs light up to display the degree of magnetic coupling betweeninductive coils 163 and 84, e.g., as determined by energy loss frominductive circuit 156, and may be used by the patient to accuratelyposition handpiece 151 relative to the implantable device. Thus, forexample, a low degree of coupling may correspond to lighting of only twoLEDs, an intermediate degree of coupling with lighting of four LEDs, anda preferred degree of coupling being reflected by lighting of all sixLEDs. Using this information, the patient may adjust the position ofhandpiece 151 over the area where implantable device is located toobtain a preferred position for the handpiece, resulting in the shortestrecharging time. In one preferred embodiment, LEDs 168 are replaced withan analog bar display on display 167, which indicates the quality ofcharge coupling.

The Monitoring and Control System

Turning to FIG. 10, the software implementing monitoring and controlsystem of FIG. 1 now described. Software 180 comprises a number offunctional blocks, schematically depicted in FIG. 10, including mainblock 184, event logging block 182, data download block 183,configuration setup block 184, user interface block 185, alarm detectionblock 186 including infection prediction block 191, sensor calibrationblock 187, firmware upgrade block 188, device identifier block 189 andstatus information block 190. The software preferably is written in C++and employs an object oriented format. In one preferred embodiment, thesoftware is configured to run on top of a Microsoft Windows® (aregistered trademark of Microsoft Corporation, Redmond, Wash.) orUnix-based operating system, such as are conventionally employed ondesktop and laptop computers. The computer running monitoring andcontrol system software 180 preferably includes a data port, e.g., USBport or comparable wireless connection, that permits handpiece 151 ofthe charging and communication system to be coupled via port 169.Alternatively, as discussed above, the computer may include a wirelesscard, e.g., conforming to the IEEE 802.11 standard, thereby enablinghandpiece 151 to communicate wirelessly with the computer runningsoftware 180. As a further alternative, the charging and communicationsystem may include telephony circuitry that automatically dials anduploads data, such as alarm data, from handpiece 151 to a secure websiteaccessible by the patient's physician.

Main block 184 preferably consists of a main software routine thatexecutes on the physician's computer, and controls overall operation ofthe other functional blocks. Main block 184 enables the physician todownload event data and alarm information stored on handpiece 151 to hisoffice computer, and also permits control and monitoring software 180 todirectly control operation of the implantable device when coupled tohandpiece 151. Main block also enables the physician to upload firmwareupdates and configuration data to the implantable device.

Event Log block 182 is a record of operational data downloaded from theimplantable device via the charging and communication system, and mayinclude, for example, pump start and stop times, motor position, sensordata for peritoneal (or pleural or pericardial) cavity and sink cavity(e.g. bladder) pressures, patient temperature, respiratory rate or fluidtemperature, pump outlet pressure, humidity, pump temperature, batterycurrent, battery voltage, battery status, and the like. The event logalso may include the occurrence of events, such as pump blockage,operation in boost or jog modes, alarms or other abnormal conditions.

Data Download block 183 is a routine that handles communication withhandpiece 151 to download data from volatile memory 154 after thehandpiece is coupled to the computer running monitoring and controlsoftware 180. Data Download block 183 may initiates, eitherautomatically or at the instigation of the physician via user interfaceblock 185, downloading of data stored in the event log.

Configuration Setup block 184 is a routine that configures theparameters stored within nonvolatile memory 71 that control operation ofthe implantable device. The interval timing parameters may determine,e.g., how long the processor remains in sleep mode prior to beingawakened to listen for radio communications or to control pumpoperation. The interval timing parameters may control, for example, theduration of pump operation to move fluid from the peritoneum (or pleuraor pericardial sac) to the sink cavity and the interval between periodictick movements that prevent blockage of the implantable device andinflow and outflow catheters. Interval timing settings transmitted tothe implantable device from monitoring and control software 180 also maydetermine when and how often event data is written to nonvolatile memory71, and to configure timing parameters used by the firmware executed byprocessor 152 of handpiece 151 of the charging and communication system.Block 184 also may be used by the physician to configure parametersstored within nonvolatile memory 71 relating to limit values onoperation of processor 70 and motor 73. These values may include minimumand maximum pressures at the inflow and outflow catheters, the maximumtemperature differential during charging, times when the pump may andmay not operate, etc. The limit values set by block 184 also configureparameters that control operation of processor 152 of handpiece 151.Block 184 also may configure parameters store within nonvolatile memory71 of the implantable device relating to control of operation ofprocessor 70 and motor 73. These values may include target daily volumesof fluid to transport, volume of fluid to be transported per pumpingsession, motor speed and duration per pumping session. Block 184 alsomay specify the parameters of operation of motor 73 during boost mode ofoperation, when coupled to handpiece 151, and shake/jog modes ofoperation when the implantable device is run using battery 74 alone.Such parameters may include motor speed and voltage, duration/number ofrevolutions of the motor shaft when alternating between forward andreverse directions, etc.

User interface block 185 handles display of information retrieved fromthe monitoring and control system and implantable device via datadownload block 183, and presents that information in an intuitive,easily understood format for physician review. As described below withrespect to FIGS. 11 to 15, such information may include status of theimplantable device, status of the charging and control system, measuredpressures, volume of fluid transported per pumping session or per day,etc. User interface block 185 also generates user interface screens thatpermit the physician to input information to configure the intervaltiming, limit and pump operation parameters discussed above with respectto block 184.

Alarm detection block 186 may include a routine for evaluating the dataretrieved from the implantable device or charging and communicationsystem, and flagging abnormal conditions for the physician's attention.For example, alarm detection block 186 may include infection predictionblock 191, which is configured to predict or detect infection based on,for example, one or more of an increase in the patient's temperatureabove a predefined threshold, an increase in the patient's respiratoryrate above a predefined threshold, and/or an increase in the fluid abovea predefined threshold. Such flags may be communicated to the physicianby changing status indicators presented by user interface block 185, orby displaying to the physician specific information about increases inthe patient's temperature, respiratory rate, or fluid viscosity via userinterface block 185.

Sensor calibration block 187 may include a routines for testing ormeasuring drift, of sensors 70, 78-81 employed in the implantabledevice, e.g., due to aging or change in humidity. Block 187 may thencompute offset values for correcting measured data from the sensors, andtransmit that information to the implantable device for storage innonvolatile memory 71. For example, pressure sensors 104 a-104 d mayexperience drift due to aging or temperature changes. Block 187accordingly may compute offset values that are then transmitted andstored in the implantable device to account for such drift.

Firmware upgrade block 188 may comprise a routine for checking theversion numbers of the processor or motor controller firmware installedon the implantable device and/or processor firmware on charging andcommunication system, and identify whether upgraded firmware exists. Ifso, the routine may notify the physician and permit the physician todownload revised firmware to the implantable device for storage innonvolatile memory 71 or to download revised firmware to the chargingand communication system for storage in nonvolatile memory 153.

Device identifier block 189 consists of a unique identifier for theimplantable device that is stored in nonvolatile memory 71 and a routinefor reading that data when the monitoring and control system is coupledto the implantable device via the charging and communication system. Asdescribed above, the device identifier is used by the implantable deviceto confirm that wireless communications received from a charging andcommunication system are intended for that specific implantable device.Likewise, this information is employed by handpiece 151 of the chargingand communication system in determining whether a received message wasgenerated by the implantable device associated with that handpiece.Finally, the device identifier information is employed by monitoring andcontrol software 180 to confirm that the handpiece and implantabledevice constitute a matched set.

Status information block 190 comprises a routine for interrogatingimplantable device, when connected via handpiece 151, to retrievecurrent status date from the implantable device, and/or handpiece 151.Such information may include, for example, battery status, the date andtime on the internal clocks of the implantable device and handpiece,version control information for the firmware and hardware currently inuse, and sensor data.

Referring now to FIGS. 11-15, exemplary screen shots generated by userinterface block 187 of software 180 are described for an ascitestreatment system. FIG. 11 shows main screen 200 that is displayed to aphysician running monitoring and control software 180. Main screen 200includes a status area that displays status information retrieved fromthe implantable device and the charging and communication system by theroutine corresponding to block 190 of FIG. 10. More particularly, thestatus area includes status area 201 for the charging and communicationsystem (referred to as the “Smart Charger) and status area 202 for theimplantable device (referred to as the “ALFA Pump”). Each status areaincludes an icon showing whether the respective system is operatingproperly, indicated by a checkmark, the device identifier for thatsystem, and whether the system is connected or active. If a parameter isevaluated by the alarm detection block 186 to be out of specification,the icon may instead include a warning symbol. Menu bar 203 identifiesthe various screens that the physician can move between by highlightingthe respective menu item. Workspace area 204 is provided below thestatus area, and includes a display that changes depending upon the menuitem selected. Below workspace area 204, navigation panel 205 isdisplayed, which includes the version number of software 180 and a radiobutton that enables the displays in workspace area 204 to be refreshed.

In FIG. 11, the menu item “Information” with submenu item “Implant” ishighlighted in menu bar 203. For this menu item selection, workspacearea 204 illustratively shows, for the implantable device, batterystatus window 204 a, measured pressures window 204 b and firmwareversion control window 204 c. Battery status window 204 a includes anicon representing the charge remaining in battery 74, and may bedepicted as full, three-quarters, one-half, one-quarter full or show analarm that the battery is nearly depleted. The time component of window204 a indicates the current time as received from the implantabledevice, where the date is expressed in DD/MM/YYYY format and time isexpressed in HR/MIN/SEC format based on a 24 hour clock. Measuredpressures window 204 b displays the bladder pressure, peritonealpressure and ambient pressures in mBar measured by sensors 104 a, 104 band 104 d respectively (see FIG. 6A). Version control window 204 cindicates the firmware version for processor 70, for the motorcontroller, and the hardware version of the implantable device. Patientparameters window 204 d displays the patient's temperature, respiratoryrate, and fluid viscosity. Alarm condition window 204 e displays anychanges in parameters that may indicate the possible development of aninfection (block 191 in FIG. 10). For example, as illustrated, alarmcondition window 204 e may alert the physician that the patient'stemperature is abnormally high, so that the physician then may follow upwith the patient regarding the possibility of infection. In someembodiments, based on information displayed in windows 204 b, 204 d,and/or 204 e, the physician may adjust the operating parameters of thepump, e.g., using the interface described below with reference to FIG.14.

Turning to FIG. 12, screen display 206 corresponding to selection of the“Smart Charger” submenu item in FIG. 11 is described. FIG. 12 includesstatus area 201 for the charging and communication system, status area202 for the implantable device, menu bar 203, workspace area 204, andnavigation panel 205 as discussed above with respect to FIG. 11. Screendisplay 206 differs from screen display 200 in that the “Smart Charger”submenu item is highlighted, and workspace area 204 displays, for thecharging and control system, battery status window 207 a and versioncontrol window 207 b. Battery status window 207 a includes an iconrepresenting the charge remaining in battery 157, and may be depicted asfull, three-quarters, one-half, one-quarter full or show an alarm thatthe battery is nearly depleted. The time component of window 207 aindicates the current time as received from handpiece 151, where thedate is expressed in DD/MM/YYYY format and time is expressed inHR/MIN/SEC format based on a 24 hour clock. Version control window 207 bindicates the firmware version for processor 152, and the hardwareversion of the charging and control system.

Referring now to FIG. 13, screen display 208 corresponding to selectionof the “Download” menu item in FIG. 11 and “Log Files” submenu item isdescribed, and implements the functionality of block 183 of software180. FIG. 13 includes status area 201 for the charging and communicationsystem, status area 202 for the implantable device, menu bar 203,workspace area 204, and navigation panel 205, all as discussed above.Screen display 208 differs from the “Information” screen display in thatthe “Log Files” submenu item is highlighted, and workspace area 204displays download progress window 209 a and storage path window 209 b.Window 209 a includes the path for the directory to which event logs maybe downloaded from the implantable device via the charging andcommunication system. Window 209 a also includes an “Open DownloadFolder” radio button that allows the physician to choose the directorypath to which the event logs are downloaded, and a progress bar that isupdated to reflect the amount of data downloaded. Window 209 b includesa radio button that can be activated to download the event log to thepath specified in window 209 a, and also includes an “Abort” radiobutton to interrupt the download process.

FIG. 14 is an exemplary depiction of screen display 210, correspondingto selection of the “Pump Settings” menu item in FIG. 11 and “FluidTransport” submenu item, and implements the functionality of blocks 184and 190 of software 180. FIG. 14 includes status area 201 for thecharging and communication system, status area 202 for the implantabledevice, menu bar 203, workspace area 204, and navigation panel 205, allas discussed above. Screen display 210 differs from the “Information”screen displays in that the “Fluid Transport” submenu item ishighlighted, and workspace area 204 includes session volume window 211a, fluid transport program window 211 b, minimum daily volume window 211c, pressure window 211 d, and a radio button in navigation panel 205that permits values entered in windows 211 a, 211 b and 211 d to betransmitted and stored in nonvolatile memory 71 of the implantabledevice. Session volume window 211 a displays the current setting for themaximum daily volume to be pumped by the implantable device, theinterval time between pumping sessions, the times of the day that thepump may be activated, the total daily pump time and the session volumeper pumping session.

The maximum daily volume displayed in window 211 a corresponds to theupper limit of fluid that the pump will transfer to the bladder in a24-hour period, although the actual volume pumped may be lower if theimplantable device detects low fluid conditions. This value is based onpatient general status and daily ascites production, and may have anallowed range, e.g., of 20 ml to 4000 ml. The interval time displayed inwindow 211 a is used by the configuration setup routine (block 184 ofFIG. 10) to compute the session volume, which preferably is in a rangeof 3 ml to 30 ml, and more preferably in a range of 10 ml to 20 ml. Thetime segments that the pump may be active, displayed in window 211 a,define the timeframes during which the implantable device can activelymove fluid to the bladder; outside of these time segments, theimplantable device will not move fluid but may implement the pump tickoperation described above to turn the gears on a regular basis toprevent clogging of the gears. The daily pump time displayed in window211 a is shown in read-only format because it is the aggregate of thetime segments entered in the time segments boxes. Finally, the sessionvolume displayed in window 211 a is computed by block 183 as the amountof fluid transferred to the bladder in a single pumping session.

Fluid transport program window 211 b displays the status of the programcontrolling operation of the pump of the implantable device based on theparameters set using block 184 of software 180. In case pump activitymust be stopped for any reason, the fluid transport program can bestopped by clicking the “Off” button in window 211 b, which will causethe Pump to stop pumping until it is manually switched back on. In oneembodiment, the fluid transport program may switched on again bypressing the “On” button in window 211 b. Because the implantable devicepreferably is implanted with the pump turned off, the physician orsurgeon may use window 211 b to turn on the fluid transport programafter the implantable device is first implanted.

Minimum daily volume window 211 c displays the expected amount of fluidto be pumped to the bladder by the implantable device, and is computedby the configuration setup routine as the session volume times thenumber of sessions per day, based on the length of the prescribed timesegments and interval timing input in window 211 a.

Pressure window 211 d of FIG. 14 permits the physician to input valuesof maximum bladder pressure and minimum peritoneal pressure that areused to control operation of the implantable pump. Thus, for example,processor 70 will command motor 73 to cease a current pumping session,or to skip a planned pumping session during the time segments identifiedin window 211 a, if the bladder pressure detected by the pressuresensors exceeds the value specified in window 211 d. Likewise, processor70 will command motor 73 to cease a current pumping session, or to skipa planned pumping session during the time segments identified in window211 a, if the peritoneal pressure detected by the pressure sensors isless than the value specified in window 211 d. If configured to operatein the above-described manner, the implantable device will neither causepatient discomfort by overfilling the patient's bladder, nor cause theperitoneal, pleural or pericardial cavity to become excessively dry.

Referring now to FIG. 15, an exemplary depiction of screen display 212,corresponding to selection of the “Test” menu item in FIG. 11 and“Manual Test Run” submenu item is described. FIG. 15 includes statusarea 201 for the charging and communication system, status area 202 forthe implantable device, menu bar 203, workspace area 204, and navigationpanel 205, all as discussed above. Screen display 212 differs from the“Information” screen displays in that the “Manual Test Run” submenu itemis highlighted, and workspace area 204 includes manual pump cycle window213. Manual pump cycle window 213 includes radio button “Start Test”which transmits a command to the implantable device via the charging andcommunication system to cause processor 70 to activate the pump for apredetermined period of time, e.g., a few seconds. Processor 70 receivespositional data from the Hall Effect sensors in motor 73 and measuredpressure data across pressure sensors 104 c and 104 d. Processor 70computes a session volume and relays that information via the chargingand communication system back to software 10, which compares themeasured data to a target session volume and provides a test result,e.g., percentage of session target volume achieved or pass/fail icon.The measured session volume, session target volume and test result aredisplayed in window 213.

Although the exemplary embodiment described above relates to a fluidmanagement system for treating chronic ascites, the fluid managementsystem of the present invention may be readily adapted for use intreating pleural or pericardial effusion. In such embodiments, it wouldbe advantageous to account for fluctuations in the pressure in thepleural or pericardial cavities arising due to respiration or normalcardiac activity, to avoid draining all fluid from the cavity andinterfering with proper lung function or cardiac activity. For a fluidmanagement system intended for treatment of pleural effusion, this maybe accomplished, for example, by programming processor 70 of theimplantable device to measure pressure in the pleural cavity over thecourse of the respiratory cycle. This information may then be used tocompute a mean pressure that is used to determine when to cease pumpingfluid from the pleural cavity. Likewise, for a fluid management systemof the present invention intended for treatment of pericardial effusion,processor 70 of the implantable device may be programmed to measurepressure in the pericardial cavity over the course of the cardiac cycle.This information may then be used to compute a mean pressure that isused to determine when to cease pumping fluid from the pericardial sac,so as to ensure some fluid remains to lubricate heart motion within thepericardial sac due to normal cardiac activity.

While various illustrative embodiments of the invention are describedabove, it will be apparent to one skilled in the art that variouschanges and modifications may be made therein without departing from theinvention. The appended claims are intended to cover all such changesand modifications that fall within the true spirit and scope of theinvention.

What is claimed:
 1. A system for noninvasive monitoring of cancerouscells of a patient having cancer, comprising: an inflow catheter havingan inlet end and an outlet end, the inlet end adapted to be positionedwithin a body cavity having an accumulation of fluid comprisingcancerous cells; an outflow catheter having an inlet end and an outletend adapted to be positioned in a bladder; an implantable pump having afirst controller, an inlet port coupled to the outlet end of the inflowcatheter and an outlet port coupled to the inlet end of the outflowcatheter, the first controller is programmed to selectively activate theimplantable pump to move the fluid comprising cancerous cells from theinlet end of the inflow catheter to the bladder during predeterminedtime periods; and an analysis station configured to analyze fluidincluding cancerous cells excreted from the bladder during urination todetermine a parameter indicative of the progress of the cancer or anefficacy of a program to treat to the cancer.
 2. The system of claim 1,wherein the inlet end of the inflow catheter is adapted to be positionedin a peritoneal cavity, a pleural cavity, or a pericardial cavity. 3.The system of claim 1, wherein the implantable device further comprisesa first pressure sensor configured to measure inflow catheter pressureand a second pressure sensor configured to measure outflow catheterpressure.
 4. The system of claim 1, wherein the implantable devicefurther comprises at least one valve that prevents reverse flow from theoutflow catheter to the inflow catheter.
 5. The system of claim 1wherein the implantable device further comprises a battery, a firsttransceiver, and a first inductive charging circuit coupled to the firstcontroller and the system further comprises: a charging andcommunication system comprising a second controller coupled to a secondtransceiver and a second inductive charging circuit, the charging andcommunication system configured to wirelessly communicate with theimplantable device via the first and second transceivers, and towirelessly transfer energy from the second inductive circuit to thefirst inductive circuit to charge the first battery.
 6. The system ofclaim 5, wherein the charging and communication system furthercomprises: a handpiece housing the second controller, the secondtransceiver, the second inductive charging circuit and a second battery;and a base containing circuitry for charging the second battery.
 7. Thesystem of claim 5, further comprising: monitoring and control softwareconfigured to run on a computer, the monitoring and control softwareconfigured to communicate operational parameters to the implantabledevice via the charging and communication system to control operation ofthe pump.
 8. The system of claim 7, wherein the first controller isprogrammed to automatically activate the pump to move fluid duringpredetermined time periods and in predetermined volumes responsive tooperational parameters communicated by the monitoring and controlsoftware.
 9. A system for noninvasive monitoring of cancerous cellscomprising: a fluid management system comprising: an implantable pumphaving a first controller; an inflow catheter having an inlet endadapted to be positioned within a body cavity and an outlet endconfigured to be coupled to the implantable pump, the body cavity havingan accumulation of fluid comprising cancerous cells; and an outflowcatheter having an inlet end configured to be coupled to the implantablepump and an outlet end adapted to be positioned in a bladder, whereinthe first controller is programmed to selectively activate theimplantable pump to move the fluid comprising cancerous cells from theinlet end of the inflow catheter to the bladder; and an analysis stationconfigured to analyze the cancerous cells.
 10. The system of claim 9,wherein the analysis station is located remotely from the fluidmanagement system.
 11. The system of claim 9, wherein the inlet end ofthe inflow catheter is adapted to be positioned in a peritoneal cavity,a pleural cavity, or a pericardial cavity.
 12. The system of claim 9,wherein the implantable device further comprises a first pressure sensorconfigured to measure inflow catheter pressure and a second pressuresensor configured to measure outflow catheter pressure.
 13. The systemof claim 9, wherein the implantable device further comprises at leastone valve that prevents reverse flow from the outflow catheter to theinflow catheter.
 14. The system of claim 9 wherein the implantabledevice further comprises a battery, a first transceiver, and a firstinductive charging circuit coupled to the first controller and the fluidmanagement system further comprises: a charging and communication systemcomprising a second controller coupled to a second transceiver and asecond inductive charging circuit, the charging and communication systemconfigured to wirelessly communicate with the implantable device via thefirst and second transceivers, and to wirelessly transfer energy fromthe second inductive circuit to the first inductive circuit to chargethe first battery.
 15. The system of claim 14, wherein the charging andcommunication system further comprises: a handpiece housing the secondcontroller, the second transceiver, the second inductive chargingcircuit and a second battery; and a base containing circuitry forcharging the second battery.
 16. The system of claim 14, furthercomprising: monitoring and control software configured to run on acomputer, the monitoring and control software configured to communicateoperational parameters to the implantable device via the charging andcommunication system to control operation of the pump.
 17. The system ofclaim 16, wherein the first controller is programmed to automaticallyactivate pump to move fluid during predetermined time periods and inpredetermined volumes responsive to operational parameters communicatedby the monitoring and control software.
 18. A method for noninvasivemonitoring of cancerous cells in a patient with cancer, the methodcomprising: pumping, via an implantable pump, bodily fluid comprisingcancerous cells from a body cavity having an accumulation of the bodilyfluid to the bladder for excretion; collecting fluid excreted from thebladder during urination; and analyzing cancerous cells contained withthe fluid to determine a parameter indicative of progress of the canceror efficacy of a cancer treatment program.
 19. The method of claim 18,further comprising analyzing the cancerous cells to assess progress of acancer treatment.
 20. The method of claim 18, wherein pumping the bodilyfluid from a the body cavity comprises pumping bodily fluid from aperitoneal cavity, a pleural cavity or a pericardial cavity.